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Record W4410251927 · doi:10.1101/2025.05.04.651923

Single-Cell Analysis of NK Cell Cytotoxicity in Cancer Therapy Using Microfluidic Droplets

2025· preprint· en· W4410251927 on OpenAlexafffund
Rumeysa Ozcan, Fatemeh Vahedi, Shina Namakian, Ali A. Ashkar, Tohid F. Didar

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldEngineering
TopicInnovative Microfluidic and Catalytic Techniques Innovation
Canadian institutionsDiscovery CentreMcMaster University
FundersCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaCanada Research Chairs
KeywordsCytotoxicityCellMicrofluidicsCancer therapyCancer cellNanotechnologyChemistryCancerCancer researchMaterials scienceMedicineInternal medicineBiochemistryIn vitro

Abstract

fetched live from OpenAlex

Abstract Natural Killer (NK) cells are critical components of the immune system, uniquely capable of detecting and eliminating cancer cells without prior sensitization. Here, a droplet-based microfluidic platform is introduced that enables real-time monitoring and single-cell analysis of NK cell-mediated cytotoxicity against K562 cancer cells. Distinct NK cells are evaluated to quantify key metrics, including the percentage of cytotoxic NK cells, serial killing capacity, killing time per target, NK-target contact duration, and migration velocities. The results demonstrated that expanded NK cells (exNK) exhibited longer attachments, superior cytotoxic activity, serial killing, and rapid killing dynamics, whereas peripheral blood NK cells (pbNK), especially when they were exposed to ascites tumor microenvironment (TME) (pbNK-asc), displayed reduced cytotoxic abilities in all parameters. Interestingly, expanded NK cells exposed to ascites TME (exNK-asc) retained partial functionality, indicating that expansion provides resilience against suppressive factors. In addition, cell velocity analysis further revealed that the presence of a cancer cell increases the migration of NK cells. This single-cell analysis provides novel insights into NK-cancer cell interactions, offering a robust framework for enhancing the efficacy of future immunotherapy applications especially for optimizing off-the-shelf NK cell-based immunotherapies. Table of Contents A droplet-based microfluidic platform examines how Natural Killer (NK) cells target cancer cells at the single-cell level. By comparing peripheral blood and expanded NK cells under normal and tumor-like conditions, distinct differences in attachment, serial killing, killing time, and migration are revealed. These findings provide insights that could enhance tumor targeting, particularly in off-the-shelf NK cell therapies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.242
Teacher spread0.221 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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